II. Molecular characterization of GRP receptors. II.A. Multiple affinity state of different cholecystokinin (CCK) receptor. CCK receptors are reported to exist in different affinity studies. To characterize these states, agonist and antagonist binding was performed on cells transfected with rat CCK-A-R, rat CCK-B-R, canine CCK-B-R and a [L355V] canine CCK-B-R mutant. Each receptor could exist in 3 affinity states and the ability to exist in multiple states was an intrinsic property of the CCK receptor. II.B. Expression and characterization of cloned human bombesin (Bn) receptors. Little is known about the pharmacology or cellular basis of action of human Bn receptors. The human GRP-R (hGRP-R) and hNMB-R were stably transfected into BALB/3T3 fibroblasts and characterized by pharmacological studies--cross-linking and intracellular activation pathways explored. These transfected cells exhibit similar pharmacology, glycosylation and changes in biologic activity with agonists to natively expressed receptors and should be useful to explore further the cellular basis of action of these peptides in humans. II.C. Chromosomal localization of CCK-A-R and CCK-B-R in humans and mouse. The CCK-A-R maps to a synteric region of human chromosome 4 and mouse chromosome 5. The CCK-B-R resides on a synteric region of human chromosome 11 and distal mouse chromosome 7. The CCK-receptors localize with 2 dopamine receptor DRD5 and DRD4 raising the possibility of coinvolvement in CNS or neuropsychiatric illness.